Individual NINDS grantees have strived to employ and develop cutting-edge genetic tools to manipulate the mouse genome to test specific hypotheses proposed in their NINDS-funded research projects. Producing many of these lines has required multiple steps in generating mouse ES cells and these lines are often laborious or difficult to obtain. The cost and time for generating such ES lines is a major bottleneck for successful animal model development as it prohibits many NINDS funded investigators from generating genetically-engineering mice, even for labs that are versed in the required advanced and very specific technologies. A central genome modification core will provide services to break the barriers to generate genetically modified mouse lines by supporting the production of designer ES-cell lines. A centralized GM Core will increase efficiency and lower the cost of generating such lines. In addition, a central service will provide opportunities for synergistic development of lines that will be of value across all user groups. The Institute has made a commitment to provide space for establishment of the GM core that would lead the way to meet the evolving needs of Neuroscience Center investigators. The major goal of the GM Core is to provide services for manipulation ofthe mouse genome in ES cells that are essential for studies ofthe mechanisms of neural function, structure and development as well as the generation of both in vitro and in vivo mouse models of diseases.